Transcriptomic Profiling of Trophoblast Subpopulations in Severe Preeclampsia Reveals Novel Aspects of RNA Dysregulation
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE93839 | GEO | 2017/01/24
SECONDARY ACCESSION(S): PRJNA362946
REPOSITORIES: GEO
Similar Datasets
Project description:Preeclampsia (PE), which affects ~8% of first pregnancies, is associated with faulty placentation. Extravillous cytotrophoblasts (CTBs) fail to differentiate properly, contributing to shallow uterine invasion and deficient spiral artery remodeling. We studied the effects of severe PE (sPE) on the smooth chorion portion of the fetal membranes. The results showed a significant expansion of the CTB layer. The cells displayed enhanced expression of stage-specific antigens that extravillous CTBs normally up regulate as they exit the placenta. Transcriptomics revealed the dysregulated expression of many genes (e.g., placental proteins, markers of oxidative stress). We confirmed a sPE-related increase in production of PAPPA1, which releases IGF-1 from its binding protein. IGF1 enhanced proliferation of smooth chorion CTBs (schCTB), a possible explanation for expansion of this layer, which may partially compensate for the placental deficits.
2016-12-10 | GSE91189 | GEO
Project description:During human pregnancy, placental cytotrophoblasts invade the uterus and its blood vessels, anchoring the progeny and rerouting maternal blood to the embryo/fetus. In preeclampsia, cytotrophoblast invasion is restricted and blood flow to the placenta is reduced. The causes of restricted cytotrophoblast invasion are unknown. Here, preeclampsia and control cytotrophoblasts were cultured for 48 h to allow differentiation/invasion. In various severe forms of preeclampsia ± intrauterine growth restriction, global transcriptional profiling revealed common aberrations in cytotrophoblast gene expression that resolved with culture. Villous cytotrophoblasts were isolated from preeclampsia placentas (PRE, n=5) and placentas of preterm labor patients without signs of infection (PTL, n=5), which served as gestation-matched controls. To better understand the CTB phenotype in the context of PE variants, we included patients with the most clinically significant forms of this condition that necessitated preterm delivery: women with severe PE ± intrauterine growth restrictions, PE with superimposed hypertension and HELLP syndrome (hemolysis, elevated liver enzymes; low platelet count). RNA was purified immediately after the cells were isolated (0 h) and after 12, 24 and 48 h in culture. The relative gene expression across the whole genome was profiled using the Affymetrix HG-U133Plus 2.0 GeneChip platform. Array quality was assesed using RMAExpress. One sample of preterm labor collected at 48h was omitted (39 arrays total). We used both LIMMA and maSigPro (R/Bioconductor) to determine differentially expressed genes.
2012-08-17 | E-GEOD-40182 | biostudies-arrayexpress
Project description:Preeclampsia complicates more than 3% of all pregnancies in the United States and Europe. High-risk populations include women with diabetes, dyslipidemia, thrombotic disorders, hyperhomocysteinemia, hypertension, renal diseases, previous preeclampsia, twin pregnancies, and low socioeconomic status. In the latter case, the incidence may increase to 20% to 25%. Preeclampsia is a major cause of maternal and fetal morbidity and mortality. Preeclampsia is defined by systolic blood pressure of more than 140 mm Hg and diastolic blood pressure of more than 90 mm Hg after 20 weeks gestation in a previously normotensive patient, and new-onset proteinuria. Abnormal placentation associated with shallow trophoblast invasion (fetal cells from outer cell layer of the blastocyst) into endometrium (decidua) and improper spiral artery remodeling in the decidua are initial pathological steps. In this study we analyzed the renin-angiotensin system in adipose tissue, decidua and placenta from women with uneventful pregnancy and women with preeclampsia. We also analyzed the tissue by Affymetrix chips in a comparison study (control vs. preeclampsia) Experiment Overall Design: 6 affymetrix human expression chips (GPL570) were analyzed. Experiment Overall Design: They represent 3 tissues (pooled from 10 individuals each) from patients with preeclampsia and from patients with uneventful pregnancy (collected by cesaraen section). Tissues from patients with uneventful pregnancy are the controls in comparison to tissues of patients with preeclampsia.
2008-06-14 | E-GEOD-6573 | biostudies-arrayexpress
Project description:Placentation requires the proper regulation of extravillous trophoblast (EVT) migration and invasion into the decidua and maternal vasculature, processes which are initiated in physiologic hypoxic conditions. Abnormal EVT migration and/or invasion have been suggested to lead to pregnancy complications, such as preeclampsia. The objectives of this study are to determine how exposure to hypoxia impacts gene expression and cellular motility of first trimester trophoblasts, and to assess if expression of migration-associated genes is dysregulated in 2nd trimester chorionic villous samples (CVS) from preeclampsia pregnancies relative to CVS from healthy pregnancies. The 1st trimester trophoblast cell line, HTR8/SVneo, was used to investigate the relationship between hypoxia and Notch signaling in trophoblast migration and invasion. RNA sequencing and quantitative RT-PCR analyses show that exposure to hypoxia (2.5% O2) activates Notch signaling in HTR-8/SVneo. We demonstrate that exposure of HTR-8/SVneo to hypoxia induces expression of genes associated with cellular migration and invasion and increases HTR-8/SVneo cellular migration and invasion, whereas inhibition of gamma-secretase decreases Notch signaling and decreases HTR-8/SVneo migration and invasion. Analysis of RNA sequencing data from CVS of preeclampsia and uncomplicated pregnancies identified significant differentially expressed genes that are involved in cellular migration and invasion. Decreased expression of migration and invasion genes in CVS from preeclampsia pregnancies, may impair trophoblast migration and invasion in the 2nd trimester of pregnancy, resulting in the development of preeclampsia.
2021-08-05 | GSE155750 | GEO
Project description:Preeclampsia (PE), which results from abnormal placentation, acts as a primary cause of maternal and neonatal morbidity and mortality. However, the cause of abnormal development of placenta remain poorly understood.Recently, it has been proposed that the genes that are differnetially expressed between PE and normal placenta tissues are associated with PE pathogenesis. To further elucidate the pathogenesis, we conducted transcriptional profiling of mRNA between PE and normal placenta tissues.
2023-04-23 | GSE149812 | GEO
Project description:4 chorionic villus sampling specimens in pregnancies destined for preeclampsia and 8 matched controls were analyzed 36 genes were differentially expressed using J5 score and prediction modeling in caGEDA computer program Keywords: snap frozen, banked CVS specimens with known pregnancy outcomes revealed genes differentially expressed in preeclampsia pregnancies
2008-11-25 | GSE12767 | GEO
Project description:Preeclampsia complicates more than 3% of all pregnancies in the United States and Europe. High-risk populations include women with diabetes, dyslipidemia, thrombotic disorders, hyperhomocysteinemia, hypertension, renal diseases, previous preeclampsia, twin pregnancies, and low socioeconomic status. In the latter case, the incidence may increase to 20% to 25%. Preeclampsia is a major cause of maternal and fetal morbidity and mortality. Preeclampsia is defined by systolic blood pressure of more than 140 mm Hg and diastolic blood pressure of more than 90 mm Hg after 20 weeks gestation in a previously normotensive patient, and new-onset proteinuria. Abnormal placentation associated with shallow trophoblast invasion (fetal cells from outer cell layer of the blastocyst) into endometrium (decidua) and improper spiral artery remodeling in the decidua are initial pathological steps. In this study we analyzed the renin-angiotensin system in adipose tissue, decidua and placenta from women with uneventful pregnancy and women with preeclampsia. We also analyzed the tissue by Affymetrix chips in a comparison study (control vs. preeclampsia) Keywords: disease comparison, disease state
2007-01-01 | GSE6573 | GEO
Project description:We investigated the DNA methylation and gene expression of 20 chorionic villi samples from early onset preeclampsia placentas to 20 gestational age matched controls. From this we were able to see a widespread disregulation in DNA methylation across a subset of genes in the genome. This may help to elucidate the underlying biological problems that lead to early onset preeclampsia. We noted that there were DNA methylation changes in many genes of importance as well as in different genomic elements such as enhancers. RNA from 8 Early Onset Preeclampsia placentas and 8 gestational age matched controls
2013-06-21 | E-GEOD-44711 | biostudies-arrayexpress
Project description:4 chorionic villus sampling specimens in pregnancies destined for preeclampsia and 8 matched controls were analyzed; 36 genes were differentially expressed using J5 score and prediction modeling in caGEDA computer program Experiment Overall Design: case-control comparisons
2008-11-29 | E-GEOD-12767 | biostudies-arrayexpress
Project description:Preeclampsia (PE), which affects 4-8% of human pregnancies, causes significant maternal and neonatal morbidity and mortality. Within the basal plate, placental cytotrophoblasts (CTBs) of fetal origin invade the uterus and extensively remodel the maternal vasculature. In PE, CTB invasion is often shallow, and vascular remodeling is rudimentary. To better understand possible causes, we conducted a global analysis of gene expression at the maternal-fetal interface in placental samples from women with PE (n = 12; 24-36 wk) vs. samples from women who delivered due to preterm labor with no evidence of infection (n = 11; 24-36 wk), a condition that our previous work showed is associated with normal CTB invasion. Using the HG-U133A&B Affymetrix GeneChip platform, and statistical significance set at log odds-ratio of B >0, 55 genes were differentially expressed in PE. They encoded proteins previously associated with PE [e.g. Flt-1 (vascular endothelial growth factor receptor-1), leptin, CRH, and inhibin] and novel molecules [e.g. sialic acid binding Ig-like lectin 6 (Siglec-6), a potential leptin receptor, and pappalysin-2 (PAPP-A2), a protease that cleaves IGF-binding proteins]. We used quantitative PCR to validate the expression patterns of a subset of the genes. At the protein level, we confirmed PE-related changes in the expression of Siglec-6 and PAPP-A2, which localized to invasive CTBs and syncytiotrophoblasts. Notably, Siglec-6 placental expression is uniquely human, as is spontaneous PE. The functional significance of these novel observations may provide new insights into the pathogenesis of PE, and assaying the circulating levels of these proteins could have clinical utility for predicting and/or diagnosing PE. Keywords: disease state analysis Basal plate biopsies of preterm labor (24-36 weeks; n=11) and preterm severe preeclampsia (24-36 weeeks; n=12) were isolated and the global gene expression profiles determined using Affymetrix Human GeneChips. Comparisons between the preeclampsia samples and the preterm labor controls revealed genes differentially expressed in preeclampsia.
2009-02-06 | E-GEOD-14722 | biostudies-arrayexpress